A new kind of highly specific irreversible enzyme inactivator is applied to a study of the neuropharmacology of enzymes involved in the neurotransmitter metabolism. These inhibitors called kcat inhibitors, required catalytic conversion by the target enzyme prior to inactivating it. The enzyme thus commits "suicide" with a specifically constructed substrate. The high specificity of these inhibitors enables the construction of models for molecular diseases. In this grant we apply these inhibitors to an in vitro and in vivo study of gamma-aminobutryric acid (GABA) transaminase, glutamate decarboxylase and monoamine oxidase. The former two inhibitors will be used in a gabanergic tissue culture system to construct "mutants" of these cells which cannot produce or over-produce their neurotransmitters GABA. The effects of these lesions on neuronal survial and competent synapse formation will be studied. The radioactively labeled glutamate decarboxylase inhibitor will be used to selectively label gabanergic cells in culture and in mouse cerebellum. It is hoped that the use of this technique coupled with autoradiography will allow for the selective mapping of gabanergic neuronal convectivity.